Cyano intermediates for prostaglandins

ABSTRACT

Intermediates for preparing prostaglandins, represented by the formula ##STR1## wherein L 3  represents ##STR2## and wherein R 25  is hydrogen or tetrahydropyranyl or similar group as defined herein. These cyano intermediates are useful intermediates in preparing prostaglandin analogs having pharmacological utility.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a division of copending application Ser. No. 566,356filed Apr. 9, 1975 now issued as U.S. Pat. No. 3,974,146.

BACKGROUND OF THE INVENTION

This invention relates to intermediates useful in the preparation ofprostaglandins and to a process for preparing them.

The essential material for this application, including the background ofthe invention, the disclosure of the invention, and the description ofthe preferred embodiments, including Preparations and Examples, isincorporated by reference from U.S. Pat. No. 3,974,146, issued to DavidR. White on Aug. 10, 1976, columns 1-31 inclusive, under the provisionsof M.P.E.P. 608.01(p).

SUMMARY OF THE INVENTION

It is the purpose of this invention to provide novel intermediatesuseful in the preparation of prostaglandins commercially in substantialamount, with high purity, and at reasonable cost. It is a furtherpurpose to provide processes for preparing these intermediates and forutilizing them.

Reference to Charts A and B will make clear the steps by which theseprocesses are performed and by which these compounds are obtained. Inthese charts, R₁₂, R₁₆, R₂₁, R₂₃, s, T, L₁, L₂, and ˜ are defined: R₁₂is ##STR3## WHEREIN C_(g) H_(2g) is alkylene of one to 9 carbon atoms,inclusive, with one to 5 carbon atoms, inclusive, in the chain between--CR₁₃ R₁₄ -- and terminal methyl; wherein R₁₃ and R₁₄ are hydrogen,alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same ordifferent, with the proviso that R₁₃ is fluoro only when R₁₄ is hydrogenor fluoro; wherein T is alkyl of one to 4 carbon atoms, inclusive,##STR4## fluoro, chloro, trifluoromethyl, or --OR₁₅, wherein R₁₅ ishydrogen or alkyl of one to 4 carbon atoms, inclusive, and s is zero,one, 2, or 3, with the proviso that not more than two T's are other thanalkyl; and wherein Z represents an oxa atom (--O--) or C_(j) H_(2j),wherein C_(j) H_(2j) is a valence bond or alkylene of one to 9 carbonatoms, inclusive, substituted with zero, one, or 2 fluoro, with one to 6carbon atoms, inclusive, between --CR₁₃ R₁₄ -- and the ring; R₁₆ is1-ethoxyethyl, tetrahydropyranyl, tetrahydrofuranyl, or a group of theformula ##STR5## wherein R₁₇ is alkyl of one to 17 carbon atoms,inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7to 12 carbon atoms, inclusive, phenyl, or phenyl substituted with one,2, or 3 alkyl of one to 4 carbon atoms, inclusive, wherein R₁₈ and R₁₉are the same or different, being hydrogen, alkyl of one to 4 carbonatoms, inclusive, phenyl or phenyl substituted with one, 2, or 3 alkylof one to 4 carbon atoms, inclusive, or, when R₁₈ and R₁₉ are takentogether, --(CH₂)_(a) -- or --(CH₂)_(b) --O--(CH₂)_(c) -- wherein a is3, 4, or 5, b is one, 2, or 3, and c is one, 2, or 3 with the provisothat b plus c is 2, 3, or 4, and wherein R₂₀ is hydrogen or phenyl; R₂₁is (1) R₁₆ as defined above or (2) carboxyacyl --C(O)R₂₂ wherein R₂₂ ishydrogen or alkyl of one to 17 carbon atoms, inclusive; R₂₃ is hydrogenor alkyl of one to 4 carbon atoms, inclusive; L₁ represents ##STR6## l₂represents ##STR7##or wherein R₁₆ is as defined above; and ˜ indicatesattachment to the cyclopropane ring in endo or exo configuration.

Included in the novel compounds of this invention is an optically activecompound of the formula ##STR8## or a mixture of that compound and theenantiomer thereof, wherein L₃ represents ##STR9## wherein R₂₅ ishydrogen or R₁₆ as defined above, with the proviso that both R₂₅ 's arethe same; said compound accordingly including compounds XV and XVII ofChart B and no others.

I claim:
 1. An optically active compound of the formula ##STR10##or amixture of that compound and the enantiomer thereof, wherein L₃represents ##STR11##and wherein R₂₅ is hydrogen, 1-ethoxyethyl,tetrahydropyranyl, tetrahydrofuranyl, or a group of the formula##STR12##wherein R₁₇ is alkyl of one to 17 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl or phenyl substituted with one, 2, or 3 alkylof one to 4 carbon atoms, inclusive, wherein R₁₈ and R₁₉ are the same ordifferent, being hydrogen, alkyl of one to 4 carbon atoms, inclusive,phenyl or phenyl substituted with one, 2, or 3 alkyl of one to 4 carbonatoms, inclusive, or, when R₁₈ and R₁₉ are taken together, --(CH₂)_(a)-- or --(CH₂)_(b) --O--(CH₂)_(c) -- wherein a is 3, 4, or 5, b is one,2, 3, and c is one, 2, or 3 with the proviso that b plus c is 2, 3, or4, and wherein R₂₀ is hydrogen or phenyl; with the further proviso thatboth R₂₅ 's are the same.
 2. An optically active compound according toclaim
 1. 3. A compound according to claim 1 wherein R₂₅ is hydrogen. 4.A compound according to claim 1 wherein R₂₅ is 1-ethoxyethyl,tetrahydropyranyl, tetrahydrofuranyl, or a group of the formula##STR13##wherein R₁₇ is alkyl of one to 17 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, or phenyl substituted with one, 2, or 3 alkylof one to 4 carbon atoms, inclusive, wherein R₁₈ and R₁₉ are the same ordifferent, being hydrogen, alkyl of one to 4 carbon atoms, inclusive,phenyl or phenyl substituted with one, 2, or 3 alkyl of one to 4 carbonatoms inclusive, or, when R₁₈ and R₁₉ are taken together, --(CH₂)_(a) --or --(CH₂)_(b) --O--(CH₂)_(c--) wherein a is 3, 4, or 5, b is one, 2, 3,and c is one, 2, or 3 with the proviso that b plus c is 2, 3, or 4, andwherein R₂₀ is hydrogen or phenyl.
 5. A compound according to claim 4wherein R₂₅ is 1-ethoxyethyl.